Non-obese diabetic (NOD) mice are genetically susceptible to experimental autoimmune prostatitis (EAP)

Rodents develop inflammatory, non-infectious, prostatitis upon autoimmuniza tion with male accessory gland (MAG) extracts in complete Freund's adjuvant (CFA). Although there appears to be differences among strains, with respec t to susceptibility to induction, specific details are not known about the genetic bases of such differences. Because NOD mice have inherited a geneti c predisposition to autoimmune lesions affecting, apart from the islets of Langerhans, a large array of secretory glands such as salivary glands, thyr oid, parathyroids and adrenal cortex, we selected this strain to assess the influence of inherited genes upon experimentally-induced autoimmune prosta titis (EAP). Indeed, MAG extracts injected into young NOD males in associat ion with CFA cause a severe inflammatory reaction in the prostate, accompan ied by a humoral and T cell-mediated response. NOD mice develop a more aggr essive form of EAP than Wistar rats, the strain of reference used to establ ish the model. In NOD mice, disease begins earlier, affects 100% of the ani mals, does not require boosting and leads to florid infiltrates circumscrib ed to lateral and dorsal prostatic lobes. Immune mice develop a T cell-medi ated response to MAG assessed by in vitro proliferation and accompanied by the release of IFN-gamma, whereas IL-4 is not detectable in the same cultur e supernatants. To assess the influence of the NOD background genes upon EA P susceptibility, we tested C57BL/6.H2(g7) mice in parallel. NOD mice are c onsiderably more susceptible to EAP induction than congenic C57BL/6.H2(g7) mice. Both strains demonstrate a detectable humoral and cell-mediated respo nse against MAG, but the histopathological manifestations are considerably more dramatic in NOD than in the C57BL/6.H2g7 strain. Our results thus supp ort the notion that NOD mice have background genes which favour severe auto immune manifestations, irrespective of the target tissue. (C) 1998 Academic Press.